Effect of sofalcone on the expression of hepatocyte growth factor (HGF) and a brief review of HGF in the stomach.
Previous studies of hepatocyte growth factor (HGF) in the stomach are briefly reviewed. Exogenous HGF has a strong effect on proliferation and migration of gastric epithelial cells. These effects of HGF are mediated by the specific receptor c-MET. Our previous immunohistochemical study revealed that the main source of endogenous HGF in human gastric ulcer is gastric fibroblasts. These findings suggest that HGF may play an important role in the repair of gastric ulcers through a paracrine mechanism. Therefore, regulation of HGF expression by gastric fibroblasts may be important. We have demonstrated that prostaglandins (PGs) E1 and E2 strongly stimulate HGF expression by gastric fibroblasts, indicating that the clinical efficacy of PGs is mediated by HGF, PGE1 actually facilitates restitution in an in vitro gastric mucosal model consisting of gastric epithelial cells and fibroblasts, which was completely inhibited by anti-HGF antibody. In this study we investigated the effect of an anti-ulcer drug, sofalcone, on PGE2 release and HGF expression by human gastric fibroblasts in primary culture. Sofalcone induced PGE2 release by human gastric fibroblasts in a dose-dependent manner. It also stimulated HGF expression by gastric fibroblasts, indicating that PGs induced by sofalcone increased HGF expression. These findings suggest that clinical efficacy of PGs and sofalcone might be mediated, at least in part, by HGF.
Takahashi
M
M
2nd Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Hata
Y
Y
Terano
A
A
D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology; D047188:Chalcones; D015232:Dinoprostone / Q000096:biosynthesis; D005347:Fibroblasts / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D006801:Humans; D016133:Polymerase Chain Reaction; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D013276:Stomach Ulcer / Q000188:drug therapy / Q000378:metabolism
D000897:Anti-Ulcer Agents; D047188:Chalcones; D012333:RNA, Messenger; C035032:sofalcone; D002599:Chalcone; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D015232:Dinoprostone